• Title/Summary/Keyword: Loss-differentiation

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Whole genome MBD-seq and RRBS analyses reveal that hypermethylation of gastrointestinal hormone receptors is associated with gastric carcinogenesis

  • Kim, Hee-Jin;Kang, Tae-Wook;Haam, Keeok;Kim, Mirang;Kim, Seon-Kyu;Kim, Seon-Young;Lee, Sang-Il;Song, Kyu-Sang;Jeong, Hyun-Yong;Kim, Yong Sung
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.1.1-1.14
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    • 2018
  • DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

Detection of Human Papillomavirus and Expression of MHC Class I in Laryngeal Squamous Cell Carcinoma (후두편평세포암종에서 Human papillomavirus의 검출과 주조직적합복합체(Major Histocompatibility Complex: MHC) Class I 발현양상)

  • Oh, Byung-Kwon;Hwang, Chan-Seung;Hong, Young-Ho;Kim, Hoon;Kim, Chun-Gil;Min, Hun-Ki
    • Korean Journal of Bronchoesophagology
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    • v.3 no.1
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    • pp.70-78
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    • 1997
  • The development of preneoplastic and neoplastic squamous cell proliferations of body sites such as the skin, female lower genital tract, and larynx is strongly associated with specific types of human papillomaviruses (HPV). Antitumor $CD^{8+}$ cells recognize peptide antigens presented on the surface of tumor cells by major histocompatibility complex (MHC) class I molecules. The MHC class I molecule is a heterodimer composed of an integral membrane glycoprotein designated the alpha chain and a noncovalently associated, soluble protein called beta-2-microglobulin( $\beta$ -2-m). Loss of $\beta$-2-m generally eliminates antigen recognition by antitumor $CD^{8+}$ T cells. We evaluated the expression of $\beta$-2-m as a potential means of tumor escape from immune recognition and the presence of HPV DNA as a cause of laryngeal squamous cell carcinomas (SCCs). Laryngeal SCCs (n=39) were analyzed for MHC class I expression by immunohistochemistry and for presence of HPV by in situ hybridization technique. The results were as follows : 1) HPV DNA was detected in 10 (25.64%) out of 39 cases in laryngeal squamous cell carcinomas. 2) MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions. 3) The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement. In conclusion, HPV was thought to be the etiological factor of SCC of larynx, and we found that the down-regulation of MHC class I was a common phenomenon In laryngeal SCC and may provide a way for tumor cells to escape from immune surveillance.

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Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells

  • Xu, Qian;Liu, Zhihua;Guo, Ling;Liu, Rui;Li, Rulei;Chu, Xiang;Yang, Jiajia;Luo, Jia;Chen, Faming;Deng, Manjing
    • Molecules and Cells
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    • v.42 no.11
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    • pp.763-772
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    • 2019
  • Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of $HIF-1{\alpha}$, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of $HIF-1{\alpha}$, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride ($CoCl_2$, $100{\mu}mol/L$), an agonist of $HIF-1{\alpha}$, and suppressed by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, $10{\mu}mol/L$), an antagonist of $HIF-1{\alpha}$. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF ($hVEGF_{165}$) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via $HIF-1{\alpha}$-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs.

Economic Valuation of Green Open Spaces: The Effects of Homeownership and Residential Types (도시녹지의 경제가치 평가: 소유 여부와 주택유형의 영향)

  • Choi, Andy Sungnok;Cho, Seong-Hoon
    • Environmental and Resource Economics Review
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    • v.30 no.3
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    • pp.395-433
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    • 2021
  • This paper aims to examine the effects of homeownership and residential types on the economic values of urban green spaces. Green open spaces as public goods provide positive externalities that are comprised of pecuniary and technological externalities. Seoul, South Korea, is used as a case study using choice experiments, with split-sample online respondents of 1,000. The study results evidenced that the differentiation between the two types of externalities is imperative for equitable provisions and efficient management of various urban open spaces. There is a positively significant and substantial impact of homeownership for apartment dwellers, ceteris paribus, but not for house dwellers. For apartments, the efficiency loss can be reduced by increasing green spaces up to the critical point where the marginal cost is at equilibrium with tenants' marginal values. For non-apartment houses, it is not homeownership but the monthly household income that has a significant impact on the amenity value. In general, public benefits from green spaces are equivalent to 16% to 33% of the current residential prices on average for a view or access. Different residential types do not cause a significant impact on the access values. Residential profiles for green spaces were developed, together with tailor-made policy suggestions.

Genetic diversity and phylogenetic relationship analyzed by microsatellite markers in eight Indonesian local duck populations

  • Hariyono, Dwi Nur Happy;Maharani, Dyah;Cho, Sunghyun;Manjula, Prabuddha;Seo, Dongwon;Choi, Nuri;Sidadolog, Jafendi Hasoloan Purba;Lee, Jun-Heon
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.1
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    • pp.31-37
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    • 2019
  • Objective: At least eight local duck breeds have been recognized and documented as national germplasm of Indonesia so far. It is necessary to genetically characterize the local duck breeds for aiding conservation and future improvement strategies. Thus, this study was carried out to assess genetic diversity and phylogenetic relationship of eight local duck populations of Indonesia using microsatellite markers. Methods: In total, 240 individuals (30 individuals each population) from Alabio (AL), Bayang (BY), Magelang (MG), Mojosari (MJ), Pegagan (PG), Pitalah (PT), Rambon (RM), and Turi (TR) duck populations were genotyped using 22 microsatellite markers. Results: The results showed a moderate level of genetic diversity among populations, with a total of 153 alleles detected over all loci and populations, ranging from 3 to 22 alleles per locus. Observed (Ho) and expected heterozygosity (He), as well as polymorphism information content over all loci and populations were 0.440, 0.566, and 0.513, respectively. Heterozygote deficiency in the overall populations ($F_{IT}=0.237$), was partly due to the heterozygote deficiency within populations ($F_{IS}=0.114$) and moderate level of genetic differentiation among populations ($F_{ST}=0.137$). The most diverse population was MG (He = 0.545) and the least diverse population was AL (He = 0.368). The majority of populations were relatively in heterozygote deficiency (except AL), due to inbreeding. The genetic distances, phylogenetic trees, and principal coordinates analysis concluded that the populations can be grouped into two major clusters, resulting AL, MG, and MJ in one cluster separated from the remaining populations. Conclusion: The present study revealed a considerable genetic diversity of studied populations and thus, proper management strategies should be applied to preserve genetic diversity and prevent loss of alleles.

Dietary 25(OH)D3 supplementation to gestating and lactating sows and their progeny affects growth performance, carcass characteristics, blood profiles and myogenic regulatory factor-related gene expression in wean-finish pigs

  • Upadhaya, Santi Devi;Chung, Thau Kiong;Jung, Yeon Jae;Kim, In Ho
    • Animal Bioscience
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    • v.35 no.3
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    • pp.461-474
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    • 2022
  • Objective: This experiment investigated the effects of supplementing vitamin D3-fortified sow and progeny diets with 25(OH)D3 on growth performance, carcass characteristics, immunity, and pork meat quality. Methods: The present study involved the assessment of supplementing the diet of sows and their progeny with or without 25 (OH)D3 in a 2×2 factorial arrangement on the performance and production characteristics of wean-finish pigs. Forty-eight multiparous sows were assigned to a basal diet containing 2000 IU/kg vitamin D3 and supplemented without (CON) or with (TRT) 50 ㎍/kg 25 (OH)D3. At weaning, a total of 80 pigs each from CON and TRT sows were allocated to weaning and growing-finishing basal diets fortified with 2,500 and 1,750 IU/kg vitamin D3 respectively and supplemented without or with 50 ㎍/kg 25(OH)D3. Results: Sows fed 25(OH)D3-supplemented diets improved pre-weaning growth rate of nursing piglets. A significant sow and pig weaning diet effect was observed for growth rate and feed efficiency (p<0.05) during days 1 to 42 post-weaning. Pigs consuming 25(OH)D3-supplemented diets gained weight faster (p = 0.016), ate more (p = 0.044) and tended to convert feed to gain more efficiently (p = 0.088) than those fed CON diet between days 98 and 140 post-weaning. Supplemental 25(OH)D3 improved water holding capacity and reduced drip loss of pork meat, increased serum 25(OH)D3 level, produced higher interleukin-1 and lower interleukin-6 concentrations in blood circulation, downregulated myostatin (MSTN) and upregulated myogenic differentiation (MYOD) and myogenic factor 5 (MYF5) gene expressions (p<0.05). Conclusion: Supplementing vitamin D3-fortified sow and wean-finish pig diets with 50 ㎍/kg 25(OH)D3 significantly improved production performance suggesting their current dietary vitamin D3 levels are insufficient. In fulfilling the total need for vitamin D, it is strongly recommended to add 50 ㎍/kg 25(OH)D3 "on top" to practical vitamin D3-fortified sow and wean-finish pig diets deployed under commercial conditions.

The effects of the Reynoutria japonica on skin-barrier and moisturizing in HaCaT cells (인간유래각질형성세포에서 호장근 추출물이 피부장벽 보호능과 보습능에 미치는 영향)

  • Eun Jeong Kang;Jia Bak;Yun-Sik Choi
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.5
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    • pp.965-976
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    • 2023
  • Reynoutria japonica is a perennate plant belonging to Polygonaceae and grows wild in East Asia containing Korea. Roots of Reynoutria japonica (R. japonica), part of roots of Reynoutria japonica, has been used for anti-inflammation and antispasmodics and contains emodin as active compound. Epidermis of skin is crucial roles to defense our body against stimulants, harmful substance and prevent water loss. In this study, we examined the effect of R. japonica and emodin, its active compound, on skin-barrier and moisturizing on HaCaT cells. First, antioxidant effect of R. japonica was prominent by scavenging ABTS+ radicals. Next, we conducted real time PCR and expression of filaggrin mRNA which is crucial role in differentiation of keratinocyte increased by R. japonica and emodin dose-dependently. In addition, R. japonica and emodin significantly elevated the expression of HAS-2 mRNA which play a role in hyaluronic acid synthesis on HaCaT cells. Taken together, R. japonica containing emodin, as active compound has potential as a cosmetic material for enhancing the function of skin-barrier and moisturizing in epidermis.

MRI Predictors of Malignant Transformation in Patients with Inverted Papilloma: A Decision Tree Analysis Using Conventional Imaging Features and Histogram Analysis of Apparent Diffusion Coefficients

  • Chong Hyun Suh;Jeong Hyun Lee;Mi Sun Chung;Xiao Quan Xu;Yu Sub Sung;Sae Rom Chung;Young Jun Choi;Jung Hwan Baek
    • Korean Journal of Radiology
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    • v.22 no.5
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    • pp.751-758
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    • 2021
  • Objective: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. Materials and Methods: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. Results: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65-95%), 100% (41 out of 41; 95% CI, 91-100%), 95% (59 out of 61; 95% CI, 87-98%), and 0.966 (95% CI, 0.912-1.000), respectively. Conclusion: Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

MRI Findings in Parkinson's Disease: Radiologic Assessment of Nigrostriatal Degeneration (파킨슨병의 자기공명영상 소견: 흑질선조체 변성의 영상학적 평가)

  • Yun Jung Bae;Jong-Min Kim;Byung Se Choi;Yoo Sung Song;Yoonho Nam;Se Jin Cho;Jae Hyoung Kim;Sang Eun Kim
    • Journal of the Korean Society of Radiology
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    • v.83 no.3
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    • pp.508-526
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    • 2022
  • Parkinson's disease (PD) is a movement disorder that develops due to degenerative loss of dopaminergic cells in the substantia nigra of the midbrain. Recent advances in MRI techniques have demonstrated various imaging findings that can reflect the underlying pathophysiological processes occurring in Parkinson's disease. Many imaging studies have shown that such findings can assist in the diagnosis of Parkinson's disease and its differentiation from atypical parkinsonism. In this review, we present MRI techniques that can be used in clinical assessment, such as nigrosome imaging and neuromelanin imaging, and we provide the detailed imaging features of Parkinson's disease reflecting nigrostriatal degeneration.

Parenchymal-sparing anatomical hepatectomy based on portal ramification of the right anterior section: A prospective multicenter experience with short-term outcomes

  • Truong Giang Nguyen;Thanh Khiem Nguyen;Ham Hoi Nguyen;Hong Son Trinh;Tuan Hiep Luong;Minh Trong Nguyen;Van Duy Le;Hai Dang Do;Kieu Hung Nguyen;Van Minh Do;Quang Huy Tran;Cuong Thinh Nguyen
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.28 no.1
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    • pp.25-33
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    • 2024
  • Backgrounds/Aims: Parenchymal-sparing anatomical hepatectomy (Ps-AH) based on portal ramification of the right anterior section (RAS) is a new technique to avoid unnecessarily transecting too much liver parenchyma, especially in cases of major anatomical hepatectomy. Methods: We prospectively assessed 26 patients with primary hepatic malignancies having undergone major Ps-AH based on portal ramification of the RAS from August 2018 to August 2022 (48 months). The perioperative indications, clinical data, intra-operative index, pathological postoperative specimens, postoperative complications, and follow-up results were retrospectively evaluated. Results: Among the 26 patients analyzed, there was just one case that had intrahepatic cholangiocarcinoma The preoperative level of α-Fetoprotein was 25.2 ng/mL. All cases (100%) had Child-Pugh A liver function preoperatively. The ventral/dorsal RAS was preserved in 19 and 7 patients, respectively. The mean surgical margin was 6.2 mm. The mean surgical time was 228.5 minutes, while the mean blood loss was 255 mL. In pathology, 5 cases (19.2%) had microvascular invasion, and in the group of HCC patients, 92% of all cases had moderate or poor tumor differentiation. Six cases (23.1%) of postoperative complications were graded over III according to the Clavien-Dindo system, including in three patients resistant ascites or intra-abdominal abscess that required intervention. Conclusions: Parenchymal-sparing anatomical hepatectomy based on portal ramification of the RAS to achieve R0-resection was safe and effective, with favorable short-term outcomes. This technique can be used widely in clinical practice.